The Immunogenicity of the Tumor-Associated Antigenα-Fetoprotein Is Enhanced by a Fusion with a Transmembrane Domain

Author:

Tran Lucile12,Judor Jean-Paul1,Gauttier Vanessa1,Geist Michel2,Hoffman Chantal2,Rooke Ronald2,Vassaux Georges1,Conchon Sophie1

Affiliation:

1. INSERM U948, Biothérapies Hépatiques, CHU Hotel Dieu, 44093 Nantes Cedex, France

2. Transgene SA, Boulevard Gonthier d’Andernach, 67405 Illkirch Graffenstaden, France

Abstract

Aim. To investigate the ability of recombinant modified vaccinia virus Ankara (rMVA) vector to induce an immune response against a well-tolerated self-antigen.Methods. rMVA vectors expressing different form ofα-fetoprotein (AFP) were produced and characterized. Naïve mice were vaccinated with MVA vectors expressing the AFP antigen in either a secreted, or a membrane-bound, or an intracellular form. The immune response was monitored by an IFNΓ ELISpot assay and antibody detection.Results. Vaccination with the membrane-associated form of AFP induced a stronger CD8+T-cell response compared to the ones obtained with the MVA encoding the secreted or the intracellular forms of AFP. Moreover, the vaccination with the membrane-bound AFP elicited the production of AFP-specific antibodies.Conclusions. The AFP transmembrane form is more immunogenic. Expressing a membrane-bound form in the context of an MVA vaccination could enhance the immunogenicity of a self-antigen.

Publisher

Hindawi Limited

Subject

Health, Toxicology and Mutagenesis,Genetics,Molecular Biology,Molecular Medicine,General Medicine,Biotechnology

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